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New risk factors and new tendency for central nervous system relapse in patients with diffuse large B-cell lymphoma:a retrospective study

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Chinese Journal of Cancer 2016年第12期35卷 713-724页

作者： qing-qing cai Li-Yang Hu Qi-Rong Geng Jie Chen Zhen-Hai Lu Hui-Lan Rao qing Liu Wen-Qi Jiang Hui-Qiang Huang Tong-Yu Lin Zhong-Jun Xia State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuang-zhou 510060GuangdongP.R.China. Department of Medical Oncology Sun Yat-sen University Cancer Center651 Dongfeng Road EastGuang-zhou 510060GuangdongP.R.China. Department of Hematology Oncology Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China. Guangdong Province Key Laboratory of Arrhythmia and Elec-trophysiology Guangzhou 510120GuangdongP.R.China. Department of Radiotherapy Sun Yat-sen Memorial Hospital of Sun Yat-sen UniversityGuangzhou 510120GuangdongP.R.China. Department of Colorectal Carci-noma Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China. Department of Pathology Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China. Department of Cancer Preven-tion Research Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China.

Background: In patients with difuse large B?cell lymphoma(DLBCL), central nervous system(CNS) relapse is uncom?mon but is nearly always fatal. This study aimed to determine the risk factors for CNS relapse in DLBCL patients and to evaluate the eicacy of rituximab and intrathecal chemotherapy prophylaxis for CNS relapse ***: A total of 511 patients with newly diagnosed DLBCL treated at the Sun Yat?sen University Cancer Center between January 2003 and December 2012 were included in the study. Among these patients, 376 received R?CHOP regimen(rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment, and 135 received CHOP regimen(cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment. Intrathe?cal chemotherapy prophylaxis(methotrexate plus cytarabine) was administered to those who were deemed at high risk for CNS relapse. In the entire cohort and in the R?CHOP set in particular, the Kaplan–Meier method coupled with the log?rank test was used for univariate analysis, and the Cox proportional hazards model was used for multivariate analysis. Diferences were evaluated using a two?tailed test, and P 110 U/L(HR = 3.59, 95% CI 1.25–10.34), serum albumin(ALB) <35 g/L(HR = 3.63, 95% CI 1.25–10.51), treatment with rituxi?mab(HR = 0.34, 95% CI 0.12–0.96), and a time to complete remission ≤ 108 days(HR = 0.22, 95% CI 0.06–0.78) were independent p

关键词： Diffuse large B?cell lymphoma Central nervous system relapse Risk factor Rituximab Intrathecal chemotherapy prophylaxis

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IL-2Rα up-regulation is mediated by latent membrane protein 1 and promotes lymphomagenesis and chemotherapy resistance in natural killer/T-cell lymphoma

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Cancer Communications 2018年第1期38卷 667-676页

作者： Liang Wang Xi-wen Bi Yu-jia Zhu Ying-zhi He Qiu-yu Lai Zhong-jun Xia qing-qing cai Department of Hematology ZhuJiang HospitalSouthern Medical UniversityGuangzhou 510280GuangdongP.R.China State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangzhou 510060GuangdongP.R.China Department of Medical Oncology Sun Yat-sen University Cancer CenterGuangzhou 510060Guang-dongP.R.China Department of Radiation Oncology Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China Department of Hematologic Oncology Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China

Background:Natural killer/T-cell lymphoma(NKTCL)is a highly aggressive non-Hodgkin lymphoma often resistant to *** level of soluble IL-2 receptorα(IL-2Rα)is elevated in NKTCL patients and correlates signifi-cantly with treatment response and *** the current study we examined the potential role of IL-2Rαby over-expressing IL-2Rαin representative cell ***:Levels of IL-2Rαwere evaluated in the human natural killer cell line NK-92 and the NKTCL cell line *** vectors were used to express latent membrane protein 1(LMP1)in NK-92 cells,and IL-2Rαin both NK-92 and SNK-6 *** biological effects of these genes on proliferation,apoptosis,cell cycle distribution,and chemosensitiv-ity were ***:Expression of IL-2Rαwas significantly higher in SNK-6 cells than in NK-92 *** LMP1 in NK-92 cells remarkably up-regulated IL-2Rαlevels,whereas selective inhibitorss of the proteins in the MAPK/NF-κB pathway significantly down-regulated IL-2Rα.IL-2Rαoverexpression in SNK-6 cells promoted cell proliferation by altering cell cycle distribution,and induced resistance to gemcitabine,doxorubicin,and *** effects were reversed by an anti-IL-2Rα***:Our results suggest that LMP1 activates the MAPK/NF-κB pathway in NKTCL cells,up-regulating IL-2Rα***-2Rαoverexpression promotes growth and chemoresistance in NKTCL,making this interleukin receptor a potential therapeutic target.

关键词： Natural killer/T-cell lymphoma Latent membrane protein 1 Epstein-Barr virus Interleukin-2 receptor alpha

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BRD2 induces drug resistance through activation of the RasGRP1/Ras/ERK signaling pathway in adult T-cell lymphoblastic lymphoma

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Cancer Communications 2020年第6期40卷 245-259页

作者： Xiao-Peng Tian Jun cai Shu-Yun Ma Yu Fang Hui-Qiang Huang Tong-Yu Lin Hui-Lan Rao Mei Li Zhong-Jun Xia Tie-Bang Kang Dan Xie qing-qing cai State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhouGuangdong 510060P.R.China Department of Medical Oncology Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060P.R.China Department of Pathology Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060P.R.China Department of Hematology Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060P.R.China

Background:Adult patients with T-cell lymphoblastic lymphoma(T-LBL)are treated with high-intensity chemotherapy regimens,but the response rate is still unsatisfactory because of frequent drug *** aimed to investigate the potential mechanisms of drug resistance in adults with ***:Gene expression microarray was used to identify differential mRNA expression profiles between chemotherapy-resistant and chemotherapy-sensitive adult T-LBL ***-time PCR and immunohistochemistry were performed to detect the expression of bromodomain-containing protein 2(BRD2)and c-Myc in fresh-frozen T-LBL tissues from 85 adult *** Ras pull-down assay was performed to monitor Ras *** immunoprecipitation assays were used to analyze the binding of E2F transcription factor 1(E2F1)/BRD2 to the RAS guanyl releasing protein 1(RasGRP1)promoter *** drug resistance effect and mechanism of BRD2 were determined by both in vivo and in vitro ***:A total of 86 chemotherapy resistance-related genes in adult T-LBL were identified by gene expression *** them,BRD2 was upregulated in chemotherapy-resistant adult T-LBL tissues and associated with worse progressionfree survival and overall survival of 85 adult T-LBL ***,BRD2 suppressed doxorubicin(Dox)-induced cell apoptosis both in vitro and in *** activation of RasGRP1/Ras/ERK signaling might contribute to the Dox resistance effect of ***,OTX015,a bromodomain and extra-terminal(BET)inhibitor,reversed the Dox resistance effect of ***-derived tumor xenograft demonstrated that the sequential use of OTX015 after Dox showed superior therapeutic ***:Our data showed that BRD2 promotes drug resistance in adult T-LBL through the RasGRP1/Ras/ERK signaling *** BRD2 may be a novel strategy to improve the therapeutic efficacy and prolong survival of adults with TLBL.

关键词： T-cell Lymphoblastic Lymphoma drug resistance BRD2 MEK ERK c-Myc RasGRP1 doxorubicin OTX015 sequential treatment simultaneous treatment

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Expression and clinical value of programmed cell death-ligand 1(PD-L1)in diffuse large B cell lymphoma:a retrospective study

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Chinese Journal of Cancer 2017年第12期36卷 767-777页

作者： Li-Yang Hu Xiao-Lu Xu Hui-Lan Rao Jie Chen Ren-Chun Lai Hui-Qiang Huang Wen-Qi Jiang Tong-Yu Lin Zhong-Jun Xia qing-qing cai State Key Laboratory of Oncology in South China Collaborative Innovation Center of Cancer MedicineSun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China Department of Medical Oncology Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China Department of Medical Oncology The Fifth Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 519000GuangdongP.R.China Department of Pathology Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology Guangzhou 510120GuangdongP.R.China Department of Radiotherapy Sun Yat-sen Memorial Hospital of Sun Yat-sen UniversityGuangzhou 510120GuangdongP.R.China Department of Anesthesiology Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China Department of Hematology Oncology Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China

Background: The programmed cell death-1(PD-1)/programmed cell death-ligand 1(PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune *** large B-cell lymphoma(DLBCL) is the most common lymphoid malignancy in adults. In the present study, we aimed to detect the expression of PD-L1 in DLBCL and to analyze its relationship with ***: We reviewed medical records of 204 newly diagnosed DLBCL patients in Sun Yat-sen University Cancer Center between October 2005 and August 2012. The expression of PD-L1 in tumor tissues from these 204 patients was detected using immunohistochemical(IHC) assay. The expression of anaplastic lymphoma kinase(ALK), CD5,CD30, and C-Myc in tumor specimens from 109 patients was detected using IHC, and Epstein-Barr virus(EBV)-encoded RNAs(EBERs) were detected using fluorescence in situ hybridization. The Spearman method was used for correlation analysis. The Kaplan-Meier method with log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate ***: Of the 204 patients, 100(49.0%) were PD-L1-positive in tumor cells and 44(21.6%) were PD-L1-positive in tumor microenvironment. PD-L1 expression in tumor cells and tumor microenvironment were more common in the non-germinal center B-cell-like(GCB) subtype than in the GCB subtype(P = 0.02 and P= 0.04). Patients with PD-L1 expression in tumor microenvironment were more likely to be resistant to first-line chemotherapy when compared with the patients without PD-L1 expression in tumor microenvironment(P = 0.03). PD-L1 expression in tumor microenvironment was negatively correlated with C-Myc expression(r =-0.20, P = 0.04). No correlations were detected between PD-L1 expression and the expression of ALK, CD5, and CD30 as well as EBERs. The 5-year overall survival(OS)rates were 50.0% and 67.3% in patients with and without PD-L1 expression in tumor cells(P

关键词： Programmed cell death-ligand 1 (PD-L1) Diffuse large B-cell lymphoma C-Myc Prognosis

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Hepatitis B virus reactivation and hepatitis in diffuse large B-cell lymphoma patients with resolved hepatitis B receiving rituximab-containing chemotherapy:risk factors and survival

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Chinese Journal of Cancer 2015年第5期34卷 225-236页

作者： Kai-Lin Chen Jie Chen Hui-Lan Rao Ying Guo Hui-Qiang Huang Liang Zhang Jian-Yong Shao Tong-Yu Lin Wen-Qi Jiang De-Hui Zou Li-Yang Hu Michael Lucas Wirian qing-qing cai Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center of Cancer Medicine Department of Medical Oncology Sun Yat-sen University Cancer Center Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology Radiotherapy Department Sun Yat-sen Memorial Hospital of Sun Yat-sen University Department of Pathology Sun Yat-sen University Cancer Center Clinical Trial Center Sun Yat-sen University Cancer Center Department of Lymphoma and Myeloma University of Texas MD Anderson Cancer Center Department of Molecular Diagnostics Sun Yat-sen University Cancer Center Lymphoma and Myeloma Center Institute of Hematology and Blood Diseases Hospital State Key Lab of Experimental Method of Hematology Chinese Academy of Medical Sciences and Peking Union of Medical College

Introduction:Hepatitis B virus(HBV) reactivation has been reported in B-cell lymphoma patients with resolved hepatitis B(hepatitis B surface antigen[HBsAg]-negative and hepatitis B core antibody[HBcAb]-positive).This study aimed to assess HBV reaaivation and hepatitis occurrence in diffuse large B-cell lymphoma(DLBCL) patients with resolved hepatitis B receiving rituximab-containing chemotherapy compared with HBsAg-negative/HBcAb-negative patients to identify risk factors for HBV reaaivation and hepatitis occurrence and to analyze whether HBV reaaivation and hepatitis affect the survival of DLBCL patients with resolved hepatitis ***:We reviewed the clinical data of 278 patients with DLBCL treated with rituximab-containing therapy between January 2004 and May 2008 at Sun Yat-sen University Cancer Center,*** faaors for HBV reaaivation,hepatitis development,and survival were examined by univariate analysis using the chi-square or Fisher's exact test and by multivariate analysis using the Cox regression ***:Among the 278 patients,165 were *** these 165 patients,6(10.9%) of 55 HBcAb-positive(resolved HBV infeaion) patients experienced HBV reactivation compared with none(0%) of 110 HBcAb-negative patients(P=0.001).Patients with resolved hepatitis B had a higher hepatitis occurrence rate than HBsAg-negative/HBcAb-negative patients(21.8%vs.8.2%,P = 0.013).HBcAb positivity and elevated baseline alanine aminotransferase(ALT) levels were independent risk factors for *** the 55 patients with resolved hepatitis B,patients with elevated baseline serum ALT or aspartate aminotransferase(AST) levels were more likely to develop hepatitis than those with normal serum ALT or AST levels(P = 0.037,P = 0.005,respeaively).An elevated baseline AST level was an independent risk factor for hepatitis in these *** patients with HBV reactivation recovered after immediate antiviral therapy,and chemotherapy was *** posit

关键词：乙型肝炎病毒 B细胞淋巴瘤危险因素弥漫性患者激活化疗单抗

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Follicle stimulating hormone controls granulosa cell glutamine synthesis to regulate ovulation

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Protein & Cell 2024年第7期15卷 512-529页

作者： Kai-Hui Zhang Fei-Fei Zhang Zhi-Ling Zhang Ke-Fei Fang Wen-Xing Sun Na Kong Min Wu Hai-Ou Liu Yan Liu Zhi Li qing-qing cai Yang Wang Quan-Wei Wei Peng-Cheng Lin Yan Lin Wei Xu Cong-Jian Xu Yi-Yuan Yuan Shi-Min Zhao The Obstetrics&Gynecology Hospital of Fudan University State Key Laboratory of Genetic EngineeringFudan UniversityShanghai 200090China Shanghai Key Laboratory of Metabolic Remodeling and Children’s Hospital of Fudan UniversityShanghai 200032China School of Life Sciences and Institutes of Biomedical Sciences Fudan UniversityShanghai 200438China Department of Nutrition and Food Hygiene School of Public HealthNantong UniversityNantong 226019China Reproductive Medicine Center The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China Shanghai Fifth People’s Hospital of Fudan University Fudan UniversityShanghai 200240China Department of Animal Science and Technology Nanjing Agricultural UniversityNanjing 210014China Key Laboratory for Tibet Plateau Phytochemistry of qinghai Province College of PharmacyQinghai University for NationalitiesXining 810007China Pediatric Research Institute Children’s Hospital Affiliated to Shandong University(Jinan Children’s Hospital)Jinan 250022China

Polycystic ovary syndrome(PCOS)is the leading cause of anovulatory *** understanding of the ovulation drivers hinders PCOS ***,we report that follicle stimulating hormone(FSH)controls follicular fluid(FF)glutamine levels to determine *** ovulation starts from FF-exposing granulosa cell(GC)*** glutamine,which decreases in pre-ovulation porcine FF,elevates in PCOS patients ***-glutamine chow to elevate FF glutamine inhibits mouse GC apoptosis and induces hormonal,metabolic,and morphologic PCOS ***,follicle-development-driving FSH promotes GC glutamine synthesis to elevate FF glutamine,which maintain follicle wall integrity by inhibiting GC apoptosis through inactivating ASK1-JNK apoptotic *** and glutamine inhibit the rapture of cultured murine *** removal or ASK1-JNK pathway activation with metformin or AT-101 reversed PCOS traits in PCOS models that are induced with either glutamine or *** suggest that glutamine,FSH,and ASK1-JNK pathway are targetable to alleviate PCOS.

关键词： ovulation glutamine granulosa cells PCOS FSH

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How fertility preservation guidelines have progressed worldwide:Potential implications and inspiration

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Reproductive and Developmental Medicine 2022年第1期6卷 34-41页

作者： Min-Xin Chen Ying Zhang qing-qing cai Shuo Zhang Ran Xu Hua Chen Yu Kang Yue Wu Ri-Cheng Chian Cong-Jian Xu President Office Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200090China Fertility Preservation Center Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200090China Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200090China Department of Genetics Shanghai JIAI Genetics and IVF InstituteShanghai 200011China Department of International Law China Foreign Affairs UniversityBeijing 100032China Department of Infertility Shanghai JIAI Genetics and IVF InstituteShanghai 200011China Clinical Research Center Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200090China Center for Reproductive Medicine Shanghai 10th People's Hospital of Tongji UniversityShanghai 200072China

To summarize fertility preservation (FP) guidelines and consensus provided by medical facilities worldwide. Five reference databases (PubMed/Embase, China BioMedical Literature Database, ClinicalKey, Wanfang Data, and China Knowledge Resource Integrated) and 7 guideline databases (Guideline International Network, National Collaborating Centre for Women’s and Children’s Health, National Guideline Clearinghouse, The National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network, New Zealand Guideline Group, and Canadian Medical Association infobase) were searched. Official websites of societies were searched to find relevant guidelines and consensus, and guidelines and published systematic reviews and consensus were reviewed from inception through May 2021. A literature search was performed regarding guidance offered in professional facilities, and 304 records (including 4 in Chinese) of existing guidelines for full-text review were found. Moreover, 55 guidelines were identified after a manual search. The literature review demonstrated that FP guidance and options were unevenly distributed worldwide for women who wanted to post-pone pregnancy or had impaired fertility after gonadal toxicity. With promising cancer survival rates and diversified family decisions, more attention should be paid to the improvement and update of accessible guidelines and regulatory infrastructure to inform patients about the available options and empower them to make informed choices. Restrictions to such services can be gradually eased due to the efficacy and safety of certain FP techniques for the right candidates to initiate pregnancy conception.

关键词： Fertility preservation Cancer patient Aging Guidance

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不同给药方式下三氧化二砷对T细胞淋巴瘤EL4细胞体内及体外抑制作用

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癌症 2009年第2期28卷 155-160页

作者：高岩蔡清清李苏卜庆廖红周颖黄慧强华南肿瘤学国家重点实验室广东广州510060 中山大学肿瘤防治中心内科广东广州510060

背景与目的:体外实验证明,三氧化二砷(arsenic trioxide,As2O3)单药可抑制多种恶性淋巴瘤细胞的增殖,并呈时间依赖性和浓度依赖性。临床研究也提示,As2O3单药治疗多种病理亚型淋巴瘤有效。但目前As2O3的剂量、具体用法仍未确定。本实验... 详细信息

背景与目的:体外实验证明,三氧化二砷(arsenic trioxide,As2O3)单药可抑制多种恶性淋巴瘤细胞的增殖,并呈时间依赖性和浓度依赖性。临床研究也提示,As2O3单药治疗多种病理亚型淋巴瘤有效。但目前As2O3的剂量、具体用法仍未确定。本实验研究不同给药方式As2O3对鼠源性T细胞淋巴瘤EL4细胞体内外的抗瘤作用,旨在了解As2O3不同给药方法对T细胞淋巴瘤疗效及不良反应。方法:MTT法检测8种浓度As2O3对EL4细胞的抑制作用,流式细胞仪分析、AnnexinⅤ-FITC/PI双标记检测细胞凋亡,电镜观察凋亡形态变化。建立EL4细胞裸鼠移植瘤模型,观察不同方案腹腔注射As2O3对EL4裸鼠移植瘤的抑制作用及裸鼠的耐受情况。结果:与对照组相比,不同浓度As2O3对EL4细胞均存在直接抑制作用(P<0.05),作用72h时的IC50为1.28μmol/L。体内实验显示,4mg·(kg·d)-1×7d与2mg·(kg·d)-1×14d给药对裸鼠移植瘤的抑制作用相近,抑瘤率分别为58.8%和55.6%(P=0.351)。移植瘤组织凋亡细胞增多并可见凋亡小体生成。毒性表现主要为急性肝损害的病理学变化。结论:As2O3体外可抑制EL4细胞增殖并可以诱导细胞凋亡,在总剂量相同的情况下,4mg·(kg·d)-1×7d与2mg·(kg·d)-1×14d的给药方式对裸鼠移植瘤生长的抑制作用近似。

关键词：三氧化二砷 T细胞淋巴瘤 EIA细胞裸鼠移植瘤抑制作用

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潜伏膜蛋白1介导IL-2Rα上调促进NK/T细胞淋巴瘤的形成和化疗耐药

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癌症 2019年第7期38卷 305-316页

作者： Liang Wang Xi-wen Bi Yu-jia Zhu Ying-zhi He Qiu-yu Lai Zhong-jun Xia qing-qing cai 珠江医院血液科南方医科大学中国广东广州510280 华南肿瘤学国家重点实验室肿瘤医学协同创新中心中国广东广州510060 中山大学肿瘤防治中心肿瘤内科中国广东广州510060 中山大学肿瘤防治中心放射肿瘤科中国广东广州510060 中山大学肿瘤防治中心血液肿瘤科中国广东广州510060

背景与目的 NK/T细胞淋巴瘤(natural killer/T-cell lymphoma,NKTCL)是一种高度侵袭性的非霍奇金淋巴瘤,经常发生化疗耐药。可溶性白细胞介素-2受体α(IL-2 receptorα,IL-2Rα)在NKTCL患者中血清水平升高,并与疗效和生存期显著相关。... 详细信息

背景与目的 NK/T细胞淋巴瘤(natural killer/T-cell lymphoma,NKTCL)是一种高度侵袭性的非霍奇金淋巴瘤,经常发生化疗耐药。可溶性白细胞介素-2受体α(IL-2 receptorα,IL-2Rα)在NKTCL患者中血清水平升高,并与疗效和生存期显著相关。本研究旨在通过代表性细胞系中过表达IL-2Rα来探讨IL-2Rα的潜在作用。方法在人NK细胞系NK-92和NKTCL细胞系SNK-6中检测IL-2Rα的水平。使用慢病毒载体在NK-92细胞中表达潜伏膜蛋白1(latent membrane protein 1,LMP1),以及在NK-92和SNK-6细胞中表达IL-2Rα,分析这些基因在增殖、凋亡、细胞周期分布和化疗敏感性中的生物学功能。结果 IL-2Rα在SNK-6细胞中的表达水平显著高于NK-92细胞。在NK-92细胞中表达LMP1可以显著上调IL-2Rα水平,而MAPK/NF-κB途径相关蛋白的选择性抑制剂可以显著下调IL-2Rα。在SNK-6细胞中IL-2Rα的过表达通过改变细胞周期分布促进细胞增殖,并诱导产生对吉西他滨、多柔比星和门冬酰胺酶的耐药,这些效应可以被抗IL-2Rα抗体逆转。结论我们的研究显示,在NKTCL细胞中LMP1激活MAPK/NF-κB途径,从而上调IL-2Rα表达。IL-2Rα过表达促进NKTCL的生长和化疗耐药,表明该白细胞介素受体可作为潜在的治疗靶点。

关键词： NK/T细胞淋巴瘤潜伏膜蛋白1 Epstein–Barr病毒白细胞介素-2受体α

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细胞程序性死亡配体-1(PD-L1)在弥漫大B细胞淋巴瘤中的表达及临床价值的回顾性研究

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癌症 2018年第6期37卷 260-271页

作者： Li-Yang Hu Xiao-Lu Xu Hui-Lan Rao Jie Chen Ren-Chun Lai Hui-Qiang Huang Wen-Qi Jiang Tong-Yu Lin Zhong-Jun Xia qing-qing cai 华南肿瘤学国家重点实验室肿瘤医学协同创新中心中山大学肿瘤防治中心广东广州510060 肿瘤内科中山大学肿瘤防治中心广东广州510060 肿瘤内科中山大学附属第五医院广东广州519000 病理科中山大学肿瘤防治中心广东广州510060 广东省心电生理和心律失常重点实验室广东广州510120 放射治疗科中山大学孙逸仙纪念医院广东广州510120 手术麻醉科中山大学肿瘤防治中心广东广州510060 血液肿瘤科中山大学肿瘤防治中心广东广州510060

背景与目的细胞程序性死亡受体-1(programmed cell death-1,PD-1)/细胞程序性死亡配体-1(programmed cell death-ligand 1,PD-L1)通路会抑制T细胞的活化,在细胞和体液免疫应答的负调控中起关键作用。弥漫大B细胞淋巴瘤(diffuse large B-... 详细信息

背景与目的细胞程序性死亡受体-1(programmed cell death-1,PD-1)/细胞程序性死亡配体-1(programmed cell death-ligand 1,PD-L1)通路会抑制T细胞的活化,在细胞和体液免疫应答的负调控中起关键作用。弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)是成年人中最为常见的淋巴样恶性肿瘤,本研究旨在检测DLBCL中PD-L1的表达,并分析其与预后的关系。方法回顾分析2005年10月至2012年8月204例在中山大学肿瘤防治中心新诊断为DLBCL的患者病历资料,采用免疫组织化学(immunohistochemical,IHC)法检测204例患者肿瘤组织中PD-L1的表达。应用IHC检测109例患者肿瘤组织中的间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)、CD5、CD30和C-Myc的表达,应用荧光原位杂交技术检测EB病毒(Epstein-Barr virus,EBV)编码RNAs(EBV-encoded RNAs,EBERs)的表达。应用Spearman方法进行相关分析,采用具有对数秩检验的Kaplan-Meier法进行单因素分析,采用Cox比例风险模型进行多因素分析。结果在选取的204例患者中,100例(49.0%)患者肿瘤细胞中PD-L1呈阳性,44例(21.6%)患者肿瘤微环境中PD-L1呈阳性。与生发中心B细胞样(germinal center B-cell-like,GCB)亚型相比,肿瘤细胞和肿瘤微环境中表达PD-L1在非生发中心B细胞样亚型中更为常见(P=0.02和P=0.04)。与肿瘤微环境中不表达PD-L1的患者相比,肿瘤微环境中PD-L1表达的患者更容易对一线化疗产生耐药性(P=0.03)。肿瘤微环境中PD-L1表达与C-Myc表达呈负相关(r=-0.20,P=0.04),而PD-L1表达与ALK、CD5、CD30和EBERs的表达无相关性。此外,肿瘤细胞中有PD-L1表达和无PD-L1表达的患者的5年总生存期(overall survival,OS)分别为50.0%和67.3%(P=0.02)。肿瘤细胞中的PD-L1表达是OS的独立风险预测因素(P<0.01)。结论PD-L1在非GCB亚型中的表达比在GCB亚型中更常见。肿瘤微环境中PD-L1的表达与C-Myc的表达呈负相关。PD-L1阳性预示DLBCL患者生存期短。因此对于PD-L1表达的患者,应推荐更多的治疗策略,如抗PD-L1抗体治疗。

关键词：细胞程序性死亡配体-1(PD-L1) 弥漫大B细胞淋巴瘤 C-Myc 预后

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